Antibiotic c-3 catechol-substituted cephalosporin compounds, compositions and method of use thereof

Abstract

This invention relates to novel cephalosporin derivatives of the formula ##STR1## wherein R 1 is hydrogen, a straight, branched, or cyclic lower alkyl group having up to six carbon atoms or a radical of the formula ##STR2## in which R 3 and R 4 are each independently hydrogen, methyl or ethyl, or R 3 and R 4 , taken together with the carbon atom to which they are attached, may be a cycloalkylidene ring containing from 3 to 5 carbon atoms; R 2 is a radical selected from the group consisting of ##STR3## wherein R 5 is hydrogen or acetyl; R 6 , R 7 and R 8 each are independently C 1-5 alkyl; n is 1 or 2; and y is 1 to 5. In another aspect, this invention relates to compounds of formula I and their nontoxic pharmaeutically acceptable salts, physiologically hydrolyzable esters or solvates. Representative compounds of this invention were selected for testing and were shown to display potent antibacterial activity.

What is claimed is: 
     
       1. A compound of the formula ##STR60## wherein R 1  is hydrogen, a straight, branched, or cyclic lower alkyl group having up to six carbon atoms or a radical of the formula ##STR61## in which R 3  and R 4  are each independently hydrogen, methyl or ethyl, or R 3  and R 4 , taken together with the carbon atom to which they are attached, may be a cycloalkylidene ring containing from 3 to 5 carbon atoms; R 2  is a radical selected from the group consisting of ##STR62##  wherein R 5  is hydrogen or acetyl; R 6 , R 7  and R 8  each are independently C 1-5  alkyl; n is 1 or 2; and y is 1 to 5.   or a nontoxic pharmaceutically acceptable salt, physiologically hydrolyzable ester or solvate thereof.   
     
     
       2. A compound of claim 1 having the formula ##STR63## in which the double bond in the C-3 side chain is in the E configuration. 
     
     
       3. A compound of claim 1 having the formula ##STR64## in which the double bond in the C-3 side chain is in the Z configuration. 
     
     
       4. A compound of claim 2 in which R 2  is the radical of the formula ##STR65## 
     
     
       5. The compound of claim 4 in which R 1  is C(CH 3 ) 2  CO 2  H. 
     
     
       6. The compound of claim 4 in which R 1  is methyl. 
     
     
       7. The compound of claim 4 which R 1  is CH 2  CO 2  H. 
     
     
       8. A compound of claim 3 in which R 2  is the radical of the formula ##STR66## 
     
     
       9. The compound of claim 8 in which R 1  is C(CH 3 ) 2  CO 2  H. 
     
     
       10. The compound of claim 8 in which R 1  is methyl. 
     
     
       11. A compound of claim 2 in which R 2  is the radical of the formula ##STR67## 
     
     
       12. The compound of claim 11 in which R 1  is methyl. 
     
     
       13. The compound of claim 11 in which R 1  is C(CH 3 ) 2  CO 2  H. 
     
     
       14. A compound of claim 2 in which R 2  is the radical of the formula ##STR68## 
     
     
       15. The compound of claim 14 in which R 1  is C(CH 3 ) 2  CO 2  H. 
     
     
       16. The compound of claim 14 in which R 1  is methyl. 
     
     
       17. The compound of claim 14 in which R 1  is hydrogen. 
     
     
       18. A compound of claim 2 in which R 2  is the radical of the formula ##STR69## 
     
     
       19. The compound of claim 18 in which R 1  is hydrogen. 
     
     
       20. The compound of claim 18 in which R 1  is methyl. 
     
     
       21. The compound of claim 18 in which R 1  is C(CH 3 ) 2  CO 2  H. 
     
     
       22. A compound of claim 2 in which R 2  is the radical of the formula ##STR70## 
     
     
       23. The compound of claim 22 in which R 1  is hydrogen. 
     
     
       24. The compound of claim 22 in which R 1  is methyl. 
     
     
       25. The compound of claim 22 in which R 1  is C(CH 3 ) 2  CO 2  H. 
     
     
       26. A compound of claim 2 in which R 2  is the radical of the formula ##STR71## 
     
     
       27. The compound of claim 26 in which R 1  is C(CH 3 ) 2  CO 2  H. 
     
     
       28. The compound of claim 26 in which R 1  is methyl. 
     
     
       29. The compound of claim 26 in which R 1  is hydrogen. 
     
     
       30. A compound of claim 2 in which R 2  is the radical of the formula ##STR72## 
     
     
       31. The compound of claim 30 in which R 1  is C(CH 3 ) 2  CO 2  H. 
     
     
       32. A pharmaceutical composition comprising an antibacterial effective amount of the compound of claim 5 and a pharmaceutically acceptable carrier or diluent. 
     
     
       33. A pharmaceutical composition comprising an antibacterial effective amount of the compound of claim 6 and a pharmaceutically acceptable carrier or diluent. 
     
     
       34. A pharmaceutical composition comprising an antibacterial effective amount of the compound of claim 7 and a pharmaceutically acceptable carrier or diluent. 
     
     
       35. A pharmaceutical composition comprising an antibacterial effective amount of the compound of claim 9 and a pharmaceutically acceptable carrier or diluent. 
     
     
       36. A pharmaceutical composition comprising an antibacterial effective amount of the compound of claim 10 and a pharmaceutically acceptable carrier or diluent. 
     
     
       37. A pharmaceutical composition comprising an antibacterial effective amount of the compound of claim 12 and a pharmaceutically acceptable carrier or diluent. 
     
     
       38. A pharmaceutical composition comprising an antibacterial effective amount of a compound of claim 13 and a pharmaceutically acceptable carrier or diluent. 
     
     
       39. A pharmaceutical composition comprising an antibacterial effective amount of the compound of claim 15 and a pharmaceutically acceptable carrier or diluent. 
     
     
       40. A pharmaceutical composition comprising an antibacterial effective amount of the compound of claim 16 and a pharmaceutically acceptable carrier or diluent. 
     
     
       41. A pharmaceutical composition comprising an antibacterial effective amount of the compound of claim 17 and a pharmaceutically acceptable carrier or diluent. 
     
     
       42. A pharmaceutical composition comprising an antibacterial effective amount of the compound of claim 19 and a pharmaceutically acceptable carrier or diluent. 
     
     
       43. A pharmaceutical composition comprising an antibacterial effective amount of the compound of claim 20 and a pharmaceutically acceptable carrier or diluent. 
     
     
       44. A pharmaceutical composition comprising an antibacterial effective amount of the compound of claim 21 and a pharmaceutically acceptable carrier or diluent. 
     
     
       45. A pharmaceutical composition comprising an antibacterial effective amount of a compound of claim 23 and a pharmaceutically acceptable carrier or diluent. 
     
     
       46. A pharmaceutical composition comprising an antibacterial effective amount of the compound of claim 24 and a pharmaceutically acceptable carrier or diluent. 
     
     
       47. A pharmaceutical composition comprising an antibacterial effective amount of the compound of claim 25 and a pharmaceutically acceptable carrier or diluent. 
     
     
       48. A pharmaceutical composition comprising an antibacterial effective amount of the compound of claim 27 and a pharmaceutically acceptable carrier or diluent. 
     
     
       49. A pharmaceutical composition comprising an antibacterial effective amount of the compound of claim 28 and a pharmaceutically acceptable carrier or diluent. 
     
     
       50. A pharmaceutical composition comprising an antibacterial effective amount of the compound of claim 29 and a pharmaceutically acceptable carrier or diluent. 
     
     
       51. A pharmaceutical composition comprising an antibacterial effective amount of the compound of claim 31 and a pharmaceutically acceptable carrier or diluent. 
     
     
       52. A method for treating bacterial infection in a mammal, which comprises administering to said mammal an antibacterial effective amount of the compound of claim 5. 
     
     
       53. A method for treating a bacterial infection in a mammal, which comprises administering to said mammal an antibacterial effective amount of the compound of claim 6. 
     
     
       54. A method for treating bacterial infection in a mammal, which comprises administering to said mammal an antibacterial effective amount of the compound of claim 7. 
     
     
       55. A method for treating bacterial infection in a mammal, which comprises administering to said mammal an antibacterial effective amount of the compound of claim 9. 
     
     
       56. A method for treating bacterial infection in a mammal, which comprises administering to said mammal an antibacterial effective amount of the compound of claim 10. 
     
     
       57. A method for treating bacterial infection in a mammal, which comprises administering to said mammal an antibacterial effective amount of the compound of claim 12. 
     
     
       58. A method for treating a bacterial infection in a mammal, comprises administering to said mammal an antibacterial effective amount of the compound of claim 13. 
     
     
       59. A method for treating bacterial infection in a mammal, which comprises administering to said mammal an antibacterial effective amount of the compound of claim 15. 
     
     
       60. A method for treating bacterial infection in a mammal, which comprises administering to said mammal an antibacterial effective amount of the compound of claim 16. 
     
     
       61. A method for treating bacterial infection in a mammal, which comprises administering to said mammal an antibacterial effective amount of the compound of claim 17. 
     
     
       62. A method for treating bacterial infection in a mammal, which comprises administering to said mammal an antibacterial effective amount of the compound of claim 19. 
     
     
       63. A method for treating bacterial infection in a mammal, which comprises administering to said mammal an antibacterial effective amount of the compound of claim 20. 
     
     
       64. A method for treating a bacterial infection in a mammal, which comprises administering to said mammal an antibacterial effective amount of the compound of claim 21. 
     
     
       65. A method for treating bacterial infection in a mammal, which comprises administering to said mammal an antibacterial effective amount of the compound of claim 23. 
     
     
       66. A method for treating bacterial infection in a mammal, which comprises administering to said mammal an antibacterial effective amount of the compound of claim 24. 
     
     
       67. A method for treating bacterial infection in a mammal, which comprises administering to said mammal an antibacterial effective amount of the compound of claim 25. 
     
     
       68. A method for treating bacterial infection in a mammal, which comprises administering to said mammal an antibacterial effective amount of the compound of claim 27. 
     
     
       69. A method for treating a bacterial infection in a mammal, which comprises administering to said mammal an antibacterial effective amount of the compound of claim 28. 
     
     
       70. A method for treating a bacterial infection in a mammal, which comprises administering to said mammal an antibacterial effective amount of the compound of claim 29. 
     
     
       71. A method for treating bacterial infection in a mammal, which comprises administering to said mammal an antibacterial effective amount of the compound of claim 31.